Phosphoinositide-generated second messengers in cardiac signal transduction

Hokin and Hokin were the first to demonstrate that tissue inositol phospholipid (phosphoinositide, PI) turnover was increased by hormone treatment. Twenty years later, Michell published a seminal review in which he suggested a relationship between stimulated inositol phospholipid metabolism and Ca²⁺ mobilization. The biochemical link between these two events was subsequently identified by Berridge and colleagues as inositol trisphosphate (InsP₃), a Ca²⁺-mobilizing ligand that is formed by the breakdown of phosphatidylinositol bisphosphate (PIP₂). The other product of inositol phospholipid hydrolysis, diacylglycerol, activates a Ca²⁺-sensitive phospholipid-dependent protein kinase, protein kinase C, which has been considered as a potential regulator of cardiac ion channels, inotropic state, and gene expression. This review summarizes our current state of knowledge concerning the formation of phosphoinositide-generated second messengers in cardiac cells and their potential role in mediating functional responses in the myocardium.